Distinct TPEF/HPP1 gene methylation patterns in gastric cancer indicate a field effect in gastric carcinogenesis

Aberrant methylation of the transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene was recently reported in hyperplastic colon polyps, colorectal adenomas and carcinomas. However, there are only limited data on significance of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation in gastric adenocarcinomas.

The aim of this study was to determine the prevalence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter methylation in gastric adenocarcinomas.

Study population consists of 48 patients with gastric cancer and 11 dyspeptic patients.

Using the Methylight assay, transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene methylation was assessed in fresh frozen cancer tissue and matched tumoural-free area of patients with gastric cancer and in the gastric mucosa of dyspeptic patients.

Transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 promoter gene methylation was observed in 35 of 48 (73%) gastric adenocarcinomas, and in 27 of 48 (56%) matched tumoural-free area cases (p=0.087). In contrast, the occurrence of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 methylation was much lower in gastric mucosa of dyspeptics (1 of 11; 9%) and the difference was significant in comparison with both tumoural tissue (p=0.0001) and tumoural-free area (p=0.0047) of cancer patients. Transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 gene expression was significantly reduced in adenocarcinomas in comparison with matched tumoural-free area (p=0.022).

Our data suggest that methylation of transmembrane protein containing epidermal growth factor and folistatin domains/hyperplastic polyposis 1 is present in the majority of gastric adenocarcinomas and in the surrounding tumoural-free area, indicating that this epigenetic change may point to a field effect in the gastric mucosa.